Automated Patch Clamp Evaluation of Snake Neurotoxins and Recombinant Antibody Antivenoms
Gordon Research Conference on Ligand Recognition & Molecular Gating
Snakebite was designated Neglected Tropical Disease (NTD) status by the WHO (2017), causing 100,000 yearly deaths and around 400,000 amputations. Each snake species has a unique venom, consisting of several dozen different toxins.
The century-old, traditional technique to generate snake antivenoms involved purifying antibodies from horse blood serum following immunization with snake venom. However, there are several drawbacks: equine-human immunoreactivity and side effects; batch-to-batch variation; specific to snake venom used.
In the last decade, advances in antibody engineering have made antibody discovery and development more efficient and specific, including creating recombinant antivenom antibodies to target and neutralize key toxin peptides. One of the most medically relevant groups of snake toxins is the α-neurotoxins, targeting the nicotinic acetylcholine receptor (nAChR).
For over two decades automated patch-clamp (APC) systems, have been used to advance our understanding of ion channel biophysics, pharmacology and their roles in physiology and disease.
Here, using QPatch II and Qube 384 APC, we functionally evaluate snake venom α-neurotoxins and anti-venom, toxin-neutralising IgG monoclonal antibodies (mAbs) on the muscle-type α1-nAChR.